Comparative Study of Extremely Low-Frequency Electromagnetic Field, Radiation, and Temozolomide Administration in Spheroid and Monolayer Forms of the Glioblastoma Cell Line (T98).

Abstract

Glioblastoma is the most common primary malignant tumor of the central nervous system. The patient's median survival rate is 13.5 months, so it is necessary to explore new therapeutic approaches. Extremely low-frequency electromagnetic field (EMF) has been explored as a noninvasive cancer treatment. This study applied the EMF with previous conventional chemoradiotherapy for glioblastoma. In this study, we evaluated the cytotoxic effects of EMF (50 Hz, 100 G), temozolomide (TMZ), and radiation (Rad) on gene expression of T98 glioma cell lines in monolayer and spheroid cell cultures. Treatment with Rad and EMF significantly increased apoptosis-related gene expression compared to the control group in monolayers and spheroids (p<0.001). The expression of apoptotic-related genes in monolayers was higher than the similar spheroid groups (p<0.001). We found that treatment with TMZ and EMF could increase the gene expression of the autophagy cascade markers compared to the control group (p<0.001). Autophagy-related gene expression in spheroids was higher than in the similar monolayer group (p<0.001). We demonstrated that coadministration of EMF, TMZ, and Rad significantly reduced cell cycle and drug resistance gene expression in monolayers and spheroids (p<0.001) compared to the control group. The combinational use of TMZ, Rad and, EMF showed the highest antitumor activity by inducing apoptosis and autophagy signaling pathways and inhibiting cell cycle and drug resistance gene expression. Furthermore, EMF increased TMZ or radiation efficiency.